Trial Outcomes & Findings for Downmodulating Monocyte Activation for HIV-1 Associated Neurocognitive Disorders (HAND) (NCT NCT01600170)
NCT ID: NCT01600170
Last Updated: 2020-11-23
Results Overview
Whole blood drawn from participants were stained with fluorochrome tagged antibodies to the surface markers. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the change in percentage of monocytes expressing the specific marker (CD16) at 12 wk versus 0wk within each Period. Data is shown as fold change over 12 weeks, in percent positive monocytes expressing surface markers. Change in primary outcome measures in each treatment arm is expressed as fold change (at week 12 versus week 0). For eg. outcome measure CD14+CD16+ in atorvastatin arm shows a mean value of 1.14. This means at 12 weeks there is an increase of 0.14 fold in the percent monocyte population expressing CD14+CD16+ marker, versus 0 week. Similarly in the placebo group. If fold change in atorvastatin group is smaller than in placebo group, then the treatment had no effect.
COMPLETED
PHASE4
11 participants
Week 0 and week 12
2020-11-23
Participant Flow
Chronic HIV infected individuals on HAART (with no changes in treatment within 4 weeks of study entry), were recruited using the Penn CFAR Clinical Core database. Subject were consented by the study nurse coordinating the project. Of 46 screened subjects, 11 fulfilled the inclusion criteria and were enrolled in the study.
Participants that met the inclusion criteria were randomly assigned to 12weeks of atorvastatin (or placebo) in the first period followed by a 4week washout and then in the second period on placebo (or atorvastatin) for 12 weeks followed by washout (4weeks). Therefore each subject served as their own control.
Participant milestones
| Measure |
Atorvastatin, Then Placebo
Participants were assigned atorvastatin at different conc. (20, 40 or 60mg / day) based on HAART for 12 wks. After a washout period of 4 weeks participants received placebo tablets (matching atorvastatin), for 12 weeks followed by another washout period of 4 weeks.
|
Placebo, Then Atorvastatin
Participants were assigned placebo tablets for 12 wks. After a washout period of 4 weeks participants received atorvastatin tablets at different conc.(20, 40 or 60mg / day) based on HAART, for 12 weeks followed by another washout period of 4 weeks.
|
|---|---|---|
|
Period 1
STARTED
|
6
|
5
|
|
Period 1
COMPLETED
|
6
|
5
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
6
|
5
|
|
Period 2
COMPLETED
|
5
|
5
|
|
Period 2
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Downmodulating Monocyte Activation for HIV-1 Associated Neurocognitive Disorders (HAND)
Baseline characteristics by cohort
| Measure |
Atorvastatin Then Placebo
n=6 Participants
Participants were given Atorvastatin followed by a washout period then placebo.
1. Subjects on PI based HAART regimen were administered atorvastatin at 10mg/day X 2weeks and then 20mg/day for 10 weeks.
2. Subjects on non-PI / non-NNRTI based HAART regimen were administered 20mg/day X 2weeks and then 40mg/day X 10weeks.
3. Subjects on NNRTI based HAART regimen were administered 40mg/day X 2weeks and then 80mg/day X 10weeks.
|
Placebo Then Atorvastatin
n=5 Participants
Participants were administered Placebo tablets followed by a washout period and then Atorvastatin.
1. Subjects on PI based HAART regimen were administered atorvastatin at 10mg/day X 2weeks and then 20mg/day for 10 weeks.
2. Subjects on non-PI / non-NNRTI based HAART regimen were administered 20mg/day X 2weeks and then 40mg/day X 10weeks.
3. Subjects on NNRTI based HAART regimen were administered 40mg/day X 2weeks and then 80mg/day X 10weeks.
|
Total
n=11 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43.3 years
STANDARD_DEVIATION 13.8 • n=5 Participants
|
47.9 years
STANDARD_DEVIATION 12.0 • n=7 Participants
|
45.4 years
STANDARD_DEVIATION 12.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American
|
6 participants
n=5 Participants
|
4 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity: Non Hispanic / Latino
|
6 participants
n=5 Participants
|
5 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
5 participants
n=7 Participants
|
11 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 0 and week 12Population: Subjects received Atorvastatin or placebo for 12wks followed by 4wk washout period then switched treatment for 12 wks followed again by a washout period. The same 11 subjects were analyzed in each group.
Whole blood drawn from participants were stained with fluorochrome tagged antibodies to the surface markers. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the change in percentage of monocytes expressing the specific marker (CD16) at 12 wk versus 0wk within each Period. Data is shown as fold change over 12 weeks, in percent positive monocytes expressing surface markers. Change in primary outcome measures in each treatment arm is expressed as fold change (at week 12 versus week 0). For eg. outcome measure CD14+CD16+ in atorvastatin arm shows a mean value of 1.14. This means at 12 weeks there is an increase of 0.14 fold in the percent monocyte population expressing CD14+CD16+ marker, versus 0 week. Similarly in the placebo group. If fold change in atorvastatin group is smaller than in placebo group, then the treatment had no effect.
Outcome measures
| Measure |
Atorvastatin
n=11 Participants
Participants were given Atorvastatin depending on their HAART
1. Subjects on PI based HAART regimen were administered atorvastatin at 10mg/day X 2weeks and then 20mg/day for 10 weeks.
2. Subjects on non-PI / non-NNRTI based HAART regimen were administered 20mg/day X 2weeks and then 40mg/day X 10weeks.
3. Subjects on NNRTI based HAART regimen were administered 40mg/day X 2weeks and then 80mg/day X 10weeks.
|
Placebo
n=11 Participants
Participants were administered Placebo tablets for 12 weeks.
|
|---|---|---|
|
Change From Week 0 in Percentage of Blood Monocytes Expressing Surface Marker CD16 at 12 Weeks, as a Result of Treatment.
|
1.14 Fold change
Interval 0.73 to 1.77
|
1.51 Fold change
Interval 0.88 to 2.59
|
PRIMARY outcome
Timeframe: Week 0 and week 12Population: Subjects received Atorvastatin or placebo for 12wks followed by 4wk washout period then switched treatment for 12 wks followed again by a washout period. The same 11 subjects were analyzed in each group.
Monocyte specific inflammatory soluble factor MCP-1 was measured by Luminex in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following treatment (atorvastatin or placebo). Data is shown as fold change in concentration of MCP-1 over 12wks within each treatment period.
Outcome measures
| Measure |
Atorvastatin
n=11 Participants
Participants were given Atorvastatin depending on their HAART
1. Subjects on PI based HAART regimen were administered atorvastatin at 10mg/day X 2weeks and then 20mg/day for 10 weeks.
2. Subjects on non-PI / non-NNRTI based HAART regimen were administered 20mg/day X 2weeks and then 40mg/day X 10weeks.
3. Subjects on NNRTI based HAART regimen were administered 40mg/day X 2weeks and then 80mg/day X 10weeks.
|
Placebo
n=11 Participants
Participants were administered Placebo tablets for 12 weeks.
|
|---|---|---|
|
Change From Baseline Within Each Period in Levels of Plasma Inflammatory Marker MCP-1 in Chronic HIV+/ HAART+ Subjects Over 12 Weeks.
|
0.96 Fold change
Interval 0.82 to 1.13
|
0.87 Fold change
Interval 0.67 to 1.12
|
PRIMARY outcome
Timeframe: week 0 and week 12Population: Subjects received Atorvastatin or placebo for 12wks followed by 4wk washout period then switched treatment for 12 wks followed again by a washout period. The same 11 subjects were analyzed in each group.
Whole blood drawn from participants were stained with fluorochrome tagged antibodies to the surface marker CD163. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the change in percentage of monocytes expressing the specific marker (CD163) at 12 wk versus 0wk within each Period. Data in each treatment arm is shown as 'mean difference' at 12 weeks versus 0 week, in percent positive monocytes expressing surface marker CD163. Data is expressed as the difference of the mean values at week 12 and week 0. The negative values mean that the mean values at 12 week were lower than the mean values at 0 week.
Outcome measures
| Measure |
Atorvastatin
n=11 Participants
Participants were given Atorvastatin depending on their HAART
1. Subjects on PI based HAART regimen were administered atorvastatin at 10mg/day X 2weeks and then 20mg/day for 10 weeks.
2. Subjects on non-PI / non-NNRTI based HAART regimen were administered 20mg/day X 2weeks and then 40mg/day X 10weeks.
3. Subjects on NNRTI based HAART regimen were administered 40mg/day X 2weeks and then 80mg/day X 10weeks.
|
Placebo
n=11 Participants
Participants were administered Placebo tablets for 12 weeks.
|
|---|---|---|
|
Change From Week 0 in Percentage of Blood Monocytes Expressing Surface Marker CD163 at 12 Weeks, as a Result of Treatment.
|
-0.06 Percentage of monocytes
Interval -9.17 to 9.05
|
-5.14 Percentage of monocytes
Interval -11.94 to 1.65
|
PRIMARY outcome
Timeframe: week 0 and week 12Population: Subjects received Atorvastatin or placebo for 12wks followed by 4wk washout period then switched treatment for 12 wks followed again by a washout period. The same 11 subjects were analyzed in each group.
Whole blood drawn from participants were stained with fluorochrome tagged antibodies to the surface marker CCR2. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the change in percentage of monocytes expressing the specific marker (CCR2) at 12 wk versus 0wk within each Period. Data in each treatment arm is shown as fold change over 12 weeks, in percent positive monocytes expressing surface marker CCR2.
Outcome measures
| Measure |
Atorvastatin
n=11 Participants
Participants were given Atorvastatin depending on their HAART
1. Subjects on PI based HAART regimen were administered atorvastatin at 10mg/day X 2weeks and then 20mg/day for 10 weeks.
2. Subjects on non-PI / non-NNRTI based HAART regimen were administered 20mg/day X 2weeks and then 40mg/day X 10weeks.
3. Subjects on NNRTI based HAART regimen were administered 40mg/day X 2weeks and then 80mg/day X 10weeks.
|
Placebo
n=11 Participants
Participants were administered Placebo tablets for 12 weeks.
|
|---|---|---|
|
Change From Week 0 in Percentage of Blood Monocytes Expressing Surface Marker CCR2 at 12 Weeks, as a Result of Treatment.
|
1.60 Fold Change
Interval 0.8 to 3.21
|
0.78 Fold Change
Interval 0.52 to 1.18
|
PRIMARY outcome
Timeframe: 0 week and 12 weekPopulation: Subjects received Atorvastatin or placebo for 12wks followed by 4wk washout period then switched treatment for 12 wks followed again by a washout period. The same 11 subjects were analyzed in each group.
Monocyte specific inflammatory soluble factor sCD14 was measured by ELISA in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following treatment (atorvastatin or placebo). Data is shown as fold change in concentration of sCD14 over 12wks within each treatment period.
Outcome measures
| Measure |
Atorvastatin
n=11 Participants
Participants were given Atorvastatin depending on their HAART
1. Subjects on PI based HAART regimen were administered atorvastatin at 10mg/day X 2weeks and then 20mg/day for 10 weeks.
2. Subjects on non-PI / non-NNRTI based HAART regimen were administered 20mg/day X 2weeks and then 40mg/day X 10weeks.
3. Subjects on NNRTI based HAART regimen were administered 40mg/day X 2weeks and then 80mg/day X 10weeks.
|
Placebo
n=11 Participants
Participants were administered Placebo tablets for 12 weeks.
|
|---|---|---|
|
Change From Baseline Within Each Period in Levels of Plasma Inflammatory Marker sCD14 in Chronic HIV+/ HAART+ Subjects Over 12 Weeks.
|
0.95 Fold Change
Interval 0.8 to 1.12
|
1.04 Fold Change
Interval 0.94 to 1.16
|
SECONDARY outcome
Timeframe: 0 week and 12 weekPopulation: Subjects were assigned to Atorvastatin or placebo for 12wks followed by 4wk washout period then subjects switched treatment for 12 wks followed again by a washout period. The same 11 subjects were analyzed in each group.
Whole blood drawn from participants were stained with fluorochrome tagged antibodies to the surface marker TF. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the change in percentage of monocytes expressing the specific marker TF at 12 wk versus 0wk within each Period. Data are expressed as fold change.
Outcome measures
| Measure |
Atorvastatin
n=11 Participants
Participants were given Atorvastatin depending on their HAART
1. Subjects on PI based HAART regimen were administered atorvastatin at 10mg/day X 2weeks and then 20mg/day for 10 weeks.
2. Subjects on non-PI / non-NNRTI based HAART regimen were administered 20mg/day X 2weeks and then 40mg/day X 10weeks.
3. Subjects on NNRTI based HAART regimen were administered 40mg/day X 2weeks and then 80mg/day X 10weeks.
|
Placebo
n=11 Participants
Participants were administered Placebo tablets for 12 weeks.
|
|---|---|---|
|
Change From Week 0 to Week 12 in Percentage of Blood Monocytes Expressing Surface Marker Tissue Factor (TF), Following Treatment.
|
1.18 Fold change
Interval 0.57 to 2.42
|
1.52 Fold change
Interval 0.75 to 3.09
|
SECONDARY outcome
Timeframe: 0 week and 12 weekPopulation: Subjects were assigned to Atorvastatin or placebo for 12wks followed by 4wk washout period then subjects switched treatment for 12 wks followed again by a washout period. The same 11 subjects were analyzed in each group.
Monocyte specific inflammatory soluble factor hsCRP was measured by Quest in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following treatment (atorvastatin or placebo). Data shown as fold change at week 12 versus week 0.
Outcome measures
| Measure |
Atorvastatin
n=11 Participants
Participants were given Atorvastatin depending on their HAART
1. Subjects on PI based HAART regimen were administered atorvastatin at 10mg/day X 2weeks and then 20mg/day for 10 weeks.
2. Subjects on non-PI / non-NNRTI based HAART regimen were administered 20mg/day X 2weeks and then 40mg/day X 10weeks.
3. Subjects on NNRTI based HAART regimen were administered 40mg/day X 2weeks and then 80mg/day X 10weeks.
|
Placebo
n=11 Participants
Participants were administered Placebo tablets for 12 weeks.
|
|---|---|---|
|
Change From 0 Week in Levels of Plasma Inflammatory Marker hsCRP in Chronic HIV+/ HAART+ Subjects Over 12 Weeks, Following Treatment.
|
0.94 Fold change
Interval 0.61 to 1.44
|
1.70 Fold change
Interval 0.85 to 3.39
|
SECONDARY outcome
Timeframe: 0 week and 12 weekPopulation: Subjects were assigned to Atorvastatin or placebo for 12wks followed by 4wk washout period then subjects switched treatment for 12 wks followed again by a washout period. The same 11 subjects were analyzed in each group.
Whole blood drawn from participants were stained with fluorochrome tagged antibodies to the surface marker CD38. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the change in percentage of monocytes expressing the specific marker CD38 at 12 wk versus 0wk within each Period. Data are expressed as fold change at 12 week versus week 0.
Outcome measures
| Measure |
Atorvastatin
n=11 Participants
Participants were given Atorvastatin depending on their HAART
1. Subjects on PI based HAART regimen were administered atorvastatin at 10mg/day X 2weeks and then 20mg/day for 10 weeks.
2. Subjects on non-PI / non-NNRTI based HAART regimen were administered 20mg/day X 2weeks and then 40mg/day X 10weeks.
3. Subjects on NNRTI based HAART regimen were administered 40mg/day X 2weeks and then 80mg/day X 10weeks.
|
Placebo
n=11 Participants
Participants were administered Placebo tablets for 12 weeks.
|
|---|---|---|
|
Change From Week 0 to Week 12 in Percentage of Blood Monocytes Expressing Surface Marker CD38, Following Treatment.
|
0.98 Fold Change
Interval 0.86 to 1.12
|
1.04 Fold Change
Interval 0.86 to 1.27
|
SECONDARY outcome
Timeframe: 0 week and 12 weekPopulation: Subjects were assigned to Atorvastatin or placebo for 12wks followed by 4wk washout period then subjects switched treatment for 12 wks followed again by a washout period. The same 11 subjects were analyzed in each group.
Monocyte specific inflammatory soluble factor sCD163 was measured by ELISA in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following treatment (atorvastatin or placebo). Data are expressed as fold change at 12 week versus week 0.
Outcome measures
| Measure |
Atorvastatin
n=11 Participants
Participants were given Atorvastatin depending on their HAART
1. Subjects on PI based HAART regimen were administered atorvastatin at 10mg/day X 2weeks and then 20mg/day for 10 weeks.
2. Subjects on non-PI / non-NNRTI based HAART regimen were administered 20mg/day X 2weeks and then 40mg/day X 10weeks.
3. Subjects on NNRTI based HAART regimen were administered 40mg/day X 2weeks and then 80mg/day X 10weeks.
|
Placebo
n=11 Participants
Participants were administered Placebo tablets for 12 weeks.
|
|---|---|---|
|
Change From Week 0 in Plasma sCD163 Levels, at Week 12 Following Treatment.
|
1.08 Fold Change
Interval 0.97 to 1.2
|
1.02 Fold Change
Interval 0.85 to 1.22
|
Adverse Events
Atorvastatin
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Ronald G Collman
University of Pennsylvania School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place